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1.
K Matsushita 《The Tokai journal of experimental and clinical medicine》1985,10(5):545-549
Two-kidney, one-clip Goldblatt models were created in Wistar rats by placing a stenotic clip around the left renal artery. A converting enzyme inhibitor, captopril was started just after operation (group 1), 4 weeks (group 2) or 12 weeks after operation (group 3). The plasma and renal renin activity (PRA and RRA) were measured by radioimmunoassay. Group 1 rats, being normotensive during captopril treatment, developed hypertension after cessation of captopril. The PRA was normal, while the RRA of ischemic kidneys was higher than that of the opposite kidneys. In group 3 rats captopril corrected hypertension in 4 of 6 rats. Although after 3 months their PRA was elevated, no difference was found in the renin content of kidneys. Group 2 rats sustained hypertension despite continued captopril treatment. These data suggest that in the early and chronic stage of this type of renovascular hypertension the renin-angiotensin system may play a major role in initiating and maintaining hypertension. In the intermediate stage (group 2), another mechanism may be involved since captopril had no effect while the pattern of the PRA and RRA of group 2 was almost the same as that of group 1. 相似文献
2.
Zimmerman BG 《Clinical and experimental pharmacology & physiology》2000,27(5-6):370-377
1. Renin inhibitors may be more advantageous than either angiotensin-converting enzyme (ACE) inhibitors or angiotensin (Ang) antagonists in blocking the renin-angiotensin system (RAS) because they do not allow accumulation of either AngI or AngII in plasma. 2. Effects of i.v. administration of two human renin inhibitors (EMD 58265 and U 71038) were compared with the ACE inhibitor enalaprilat on mean blood pressure (BP), renal blood flow (RBF) and plasma AngI and AngII in the anaesthetized two-kidney one-clip Goldblatt rabbit. 3. At doses of 2-2.5 mg/kg, i.v., EMD 58265 and 5-10 mg/kg, i.v., U 71038, both drugs decreased BP approximately 10 mmHg more than enalaprilat (2-4 mg/kg, i.v.) when given either before or after the ACE inhibitor. None of the three agents had any significant effect on RBF in the face of the lowered BP; however, renal vascular resistance was decreased. A higher dose of enalaprilat (10 mg/kg, i.v.) had no further effect on BP than the lower doses but did cause a marked increase in RBF. 4. Both renin inhibitors markedly decreased plasma AngI, but the high basal level of AngII was less consistently and only modestly affected. Enalaprilat, in either the low dose range or at the high dose, was also not effective in significantly decreasing AngII. 5. The results indicate that renin inhibition in the rabbit with a high circulating AngII level is more effective in lowering BP than ACE inhibition. A high dose of the ACE inhibitor may be required to block the intrarenal RAS, which may account for the increase in RBF. 相似文献
3.
Effects of the angiotensin converting enzyme inhibitor, captopril, in essential hypertension
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1 Plasma and biliary concentrations of amoxycillin and ceftriaxone were measured after bolus intravenous administration (500 mg) in four subjects with normal hepato-biliary and renal function. 2 The mean plasma elimination half-life for ceftriaxone (t 1/2 = 330 +/- 30 min) was considerably longer than that for amoxycillin (t 1/2 = 60 +/- 9 min). 3 The biliary concentration of ceftriaxone was above plasma concentration of the drug throughout the study period, whereas amoxycillin concentration in the bile was lower than that in plasma. 4 Both plasma and biliary concentrations of ceftriaxone were substantially higher than previously determined minimum inhibitory concentration (MIC) values for E. coli (and several other common biliary tract pathogens) for over 6 h following drug administration. Amoxycillin concentration in plasma fell below MIC by 2 h, and did not reach inhibitory concentrations in bile. 相似文献
4.
In one-clip, two-kidney hypertensive models of rats, the renal arterial blood velocity was recorded using the bidirectional Doppler velocimeter before and at various times after clipping of the renal arteries. In all the rats, immediately after placement of a clip, the blood velocity of the stenosed artery was lowered significantly. Although the blood velocity remained low 2 weeks after clipping, it recovered to the pre-clip level at 6 and at 11 to 13 weeks after clipping. The plasma renin activity tended to decrease following the acute, high-renin stage of hypertension. If it can be assumed that the blood velocity is one of the indexes representing blood flow, its return to the pre-clip normal level in the chronic stage of renovascular hypertension may signify recovery of blood flow to the clipped kidney leading to a reduction in renal renin synthesis and consequently a decrease in plasma renin activity. 相似文献
5.
Control of essential hypertension with captopril, an angiotensin converting enzyme inhibitor.
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M M el-Mehairy A Shaker M Ramadan S Hamza S S Tadros 《British journal of clinical pharmacology》1981,11(5):469-475
1 Captopril, an orally active angiotensin converting enzyme inhibitor, was compared with hydrochlorothiazide (HCT) in the treatment of mild and moderate essential hypertension. 2 Twenty outpatients received no antihypertensive therapy for 2 weeks, after which they were given placebo for 8 weeks. Since their diastolic blood pressure remained above 100 mm Hg, they were then randomized to receive either captopril (twelve patients) or HCT (eight patients) for a 4-week titration period. If the supine diastolic blood pressure (SDBP) was normalized, (less than or equal to 90 mm Hg) by the end of titration period, the established regimen was continued for an 8-week maintenance period; if not, the alternate drug was added in increasing doses for up to 4 weeks and the combined therapy was maintained for the remaining 4 weeks. 3 After the first 4 weeks of therapy, both groups showed a statistically significant decrease in both systolic and diastolic blood pressure. Normalization of SDBP occurred in 75% of patients treated with captopril alone, and the addition of HCT produced normalization in the remainder. HCT alone resulted in normalization of SDBP in 50% of patients and the blood pressure of the remaining patients was normalized after the addition of captopril. 4 Captopril given orally, either alone or in conjunction with HCT, is an effective agent for the control of mild and moderate essential hypertension. 5 In our series the main side effects encountered were vertigo and dizziness, transient eosinophilia, a rise of BUN and or/a rise of SGPT or SGOT. 相似文献
6.
The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function. 总被引:2,自引:2,他引:2
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E. R. Lumbers J. H. Burrell R. I. Menzies A. D. Stevens 《British journal of pharmacology》1993,110(2):821-827
1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
K Matsushita 《The Tokai journal of experimental and clinical medicine》1984,9(4):253-258
We attempted to produce two-kidney one-clip renovascular hypertension in SD rats, using hemoclips 0.2mm in diameter. After 12 weeks, 10 of the 16 rats were hypertensive. At this point, one-kidney, one-clip models were prepared by contralateral nephrectomy in five of the 10 hypertensive rats and in all six normotensive rats. Postoperatively, these 11 rats developed hypertension. Four to 6 weeks later, the clip was removed from the renal artery in five two-kidney and 11 one-kidney hypertensive rats. After unclipping, all the rats became normotensive although the extent of the fall in blood pressure in the one-kidney model was significantly greater than in the two-kidney model. The roles of the contralateral non-clipped kidney in the evolution of two-kidney, one-clip Goldblatt hypertension appear to be dual; sometimes depressing elevated blood pressure and sometimes maintaining it. Thus, it is postulated that in the six initially normotensive rats, its action was predominantly antihypertensive, while in the other 10 hypertensive rats, the presence of a contralateral non-clipped kidney served to develop and maintain hypertension even after unclipping. 相似文献
8.
1. The influence of the intact kidney on blood pressure, extracellular fluid volume (ECF, ferrocyanide space) and ECF volume distribution was studied in rats 60 days after constriction of the contralateral renal artery. 2. Renal artery constriction increased both blood pressure and ECF levels. The rise of both variables was more pronounced in rats with the contralateral kidney removed (one-kidney rats) than with the contralateral kidney intact (two-kidney rats). 3. The interstitial fluid volume increased similarly in both experimental groups, the more pronounced ECF increase in the more severly hypertensive one-kidney rats being due to increased plasma volume. In the less hypertensive two-kidney group the plasma volume was not increased significantly but correlated positively with the blood pressure levels. 4. The plasma volume/interstitial fluid volume ratio was decreased in the two-kidney group but did not differ from control values in the one-kidney group thus resembling the ECF partition reported in the hypo-and hypervolaemic type of essential hypertension, respectively. 5. It is suggested that the antihypertensive influence of the intact kidney may be partly due to its ability to escape from the sodium-retaining mechanism activated by renal artery stenosis, which determines the degree of plasma volume expansion and, in connection with this, also the degree of blood pressure elevation. 相似文献
9.
D Morelowska E Chabielska D Pawlak A Azzadin A Bia?kowska D Krygicz W Buczko 《Polish journal of pharmacology and pharmacy》1992,44(4):365-372
In 2K,1C-RHR (two-kidney, one-clip hypertensive rats) serotonergic mechanisms in blood platelets were studied. The endogenous serotonin (5-HT) concentration in whole blood and in platelets remained unchanged in relation to the sham operated rats. Also the uptake of labelled 5-HT in rats with renal hypertension was not altered. However platelets aggregability was increased in 2K,1C-RHR. Acute administration of captopril (10 mg/kg and 100 mg/kg po) diminished blood pressure but did not change either the concentration of 5-HT in whole blood and in platelets of hypertensive rats or the uptake of this amine. Platelets aggregation and the amplifying effect of 5-HT in hypertensive rats were also unchanged after acute captopril administration. Similar results were observed after its administration in a dose of 30 mg/kg for one week. Our results indicate that captopril did not affect the platelets serotonergic mechanisms in 2K,1C-RHR. 相似文献
10.
目的:图手术期心肌缺血主要是因为应激引起冠状动脉内皮功能障碍所致,所以观察卡托普利对其影响。方法:杂种犬20只均分为4组:Ⅰ组(对照组),Ⅱ组(心肌梗塞模型组),Ⅲ组(心梗 胃大部切除术)和Ⅳ组(心梗 卡托普利 胃大部切除术)。心梗2周后行胃大部分切除术,测定Ⅲ、Ⅳ两组的基础状态、术前和术后的血流动力学指标、血浆内皮素(ET)及一氧化氮(NO)。用组织原位杂交方法观察4组非梗塞区冠脉内皮-氧化氮合酶(NOS)mRNA表达水平。结果:在Ⅲ组,手术使LV dP/dt_(max)、心脏指数(CI)及NO下降,引起LVEDP、PCWP、总外周阻力(TPR)、左室舒张压力下降时间常数(T值)和ET升高。在Ⅳ组,用卡托普利后40min,TPR下降,T值升高;手术使血流动力学指标回降,不影响其它指标。组织原位杂交示,NOS mRNA在Ⅰ组高度表达,Ⅱ组和Ⅳ组次之,Ⅲ组最低。结论:卡托普利能预防胃大部切除术引起的左室舒缩障碍和冠脉内皮功能障碍。 相似文献
11.
Effect of captopril (a converting enzyme inhibitor) on blood-brain barrier permeability and cerebral blood flow in normotensive rats 总被引:1,自引:0,他引:1
H S Sharma 《Neuropharmacology》1987,26(1):85-92
Intracarotid (10 mg/kg), intracerebroventricular (100, 200 micrograms) or topical application (0.8 M) of captopril (a converting enzyme inhibitor) increased the permeability of the blood-brain barrier to Evans blue albumin (EBA) and [131I]sodium in anesthetized normotensive rats. The permeability of the blood-brain barrier to albumen in 6 and to [131I]sodium in 10 out of 14 regions of the brain was increased in the perfused hemisphere after infusion of captopril into the right carotid artery. These regions of the brain were associated with a 54-107% increase in regional cerebral blood flow (CBF). Pretreatment with indomethacin and aprotinin prevented both the increased regional permeability of the blood-brain barrier along with regional cerebral blood flow. Pretreatment with vinblastine prevented only the regional increase in permeability of the blood-brain barrier. The regional cerebral blood flow continued to remain high. The probable mechanism(s) underlying the increased cerebral blood flow and permeability of the blood-brain barrier after infusion of captopril is discussed. 相似文献
12.
Enalapril (MK-421) is a new angiotensin converting enzyme inhibitor which effectively lowers elevated blood pressure and might also be useful in heart failure. Enalapril was infused into six awake dogs 2 hours after left circumflex coronary artery embolization (acute failure group) and into six other awake dogs two to six months after coronary embolization (chronic failure group). In the acute failure group 2 hours after embolization, increased left ventricular end-diastolic pressure and reduced cardiac output remained unchanged during enalapril infusion. In the chronic failure group, increased left ventricular end-diastolic pressure also remained unchanged during enalapril infusion, but cardiac output, which had fallen to 131.8 +/- 11.9 (S.D.) from 165.8 +/- 17.9 ml/min/kg (P less than 0.01) by two to six months in this group rose during enalapril infusion to 154.5 +/- 27.7 ml/min/kg (P less than 0.05). Heart rate and blood pressure were not changed during enalapril in either group, but stroke volume rose (26.0 +/- 5.9 to 29.2 +/- 6.9 ml, P less than 0.01) and systemic vascular resistance fell (58.5 +/- 10.3 to 39.3 +/- 4.3 units, P less than 0.01) during enalapril only in the chronic failure group. Plasma renin activity after embolization was slightly but not significantly higher in the acute failure group. Thus, enalapril appears to be an arterial vasodilator in dogs with chronic but not acute left ventricular failure. 相似文献
13.
14.
15.
Effect on different tissues with regard to angiotensin converting enzyme during captopril treatment in the rat was studied. Male Wistar-Kyoto rats (n = 9) were treated during four weeks with captopril dissolved into the drinking water at the dose 30 mg/kg/day. Control rats (n = 9) had water only. Serum angiotensin converting enzyme (ACE) activity increased three-fold during captopril treatment, and ACE of purified pulmonary plasma membranes increased about 64% (P less than 0.001) compared to untreated rats. ACE activity of membrane fractions of other tissues studied i.e. testicles, epididymes, kidneys, and small intestine brush border did not increase similarly during captopril treatment. The highest amounts of ACE was demonstrated in epididymes, but captopril did not produce increased amounts of ACE in the epididymes. The main source of increased serum ACE activity during captopril treatment appeared to be in the pulmonary tissue. 相似文献
16.
T Forslund 《Acta pharmacologica et toxicologica》1983,52(3):201-204
The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a second study rats were treated with different captopril doses (6.25 micrograms, 12.5 micrograms, 25 micrograms, 50 micrograms, and 200 micrograms/ml water) during three weeks. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneously increase of serum ACE activity during the first day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 micrograms/ml water. 相似文献
17.
P S?yn?v?lammi I P?rsti P P?rsti A K Nurmi E Sepp?l? V Manninen H Vapaatalo 《Journal of cardiovascular pharmacology》1988,12(1):88-93
Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks. At the end of the baseline period and of each month of the double-blind phase, 12 h overnight urine collections were made and morning blood samples were taken about 12 h after the last dose of medication. During the double-blind phase, blood pressure in the quinapril group (n = 7) decreased from 159 +/- 3/105 +/- 1 to 141 +/- 6/94 +/- 2 mm Hg (mean +/- SEM). Serum ACE activity and plasma angiotensin II concentration were reduced to 4 +/- 1% and 14 +/- 1% of the pretreatment values, respectively. Neither the plasma concentrations nor the urinary excretions of prostaglandin E2, 6-keto-prostaglandin F1 alpha (a prostacyclin metabolite), or thromboxane B2 (a metabolite of thromboxane A2) were affected by quinapril. In the placebo group, blood pressure tended to decline but the biochemical variables remained essentially unchanged. These results indicate that prostanoids are not involved in the antihypertensive action of quinapril, the principal effect of which seems to be inhibition of the renin-angiotensin system. 相似文献
18.
Abe F Omata K Yamada M Tsunoda K Sato T Shimizu T Ito S Abe K Nakazima M Morimoto T Takanashi N 《Immunopharmacology》1999,44(1-2):199-204
Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma was developed to evaluate the dynamics of endogenous AT II in various types of hypertension. Detection limit of this method was less than 2.3 pg/ml, and normal value is less than 25 pg/ml. Cross reactivity of antibody with AT I and III was 0.037% and 21%, respectively. There were good correlation between the value measured by direct method, and that of extraction method (r = 0.96, P < 0.01) and plasma renin activity (r = 0.80, P < 0.01). By oral administration of ACE inhibitor (captopril 50 mg), AT II levels were suppressed to 10 pg/ml or less in most patients with essential hypertension, renal parenchymal hypertension and renovascular hypertension up to 2 h. However, AT II levels in patients treated with ACE inhibitors chronically were not different from the AT II levels in patients without ACE inhibitor. In primary aldosteronism AT II was extremely low levels. AT II markedly increased by the stimulation test using furosemide (1 mg/kg i.v.). These results suggest that this method may be useful to clarify the pathophysiology of hypertension and the escape of the inhibition by ACE inhibitor. 相似文献
19.
Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.
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1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved. 相似文献
20.
1. In addition to their antihypertensive effect, ACE inhibitors have been reported to increase general well-being, general health and vitality and work performance. The cause of these effects is not known. A possible mechanism may be release of beta-endorphins. 2. In the present study changes in plasma concentration of beta-endorphins on days with ACE inhibitor treatment (n = 12) and on non-treatment control days (n = 12) were compared in 6 patients. 3. Both on control and treatment days the beta-endorphin level fell, by 7.1 and 10.0%, respectively, from 8.00 a.m. to 8.00 p.m., reflecting the known diurnal rhythm of this opioid. This difference between the control and treatment days is not statistically significant. 4. The study should be extended to determine endorphin concentration in the cerebrospinal fluid, and other opioids should be looked for. 相似文献